Final goal of our research is to regulate the IgE antibody response based on physiological mechanisms of the antibody response. Our previous studies have shown that the IgE antibody response is regulated by T cell factors having affinity for IgE. One of the IgE-binding factors selectively enhances the IgE response (IgE-potentiating factor), while another IgE-binding factor suppresses the response (IgE-suppressive factor). The two IgE-binding factors are glycopeptides which share a common structural gene and differ in their carbohydrate moieties. Evidence was obtained that the same T cells can produce both IgE-potentiating factor and IgE-suppressive factor, and that the nature of IgE-binding factors formed by the cells is decided by two T cell factors; glycosylation enhancing factor (GEF) and glycosylation inhibiting factor (GIF). It became clear that GIF is a fragment of phosphorylated lipomodulin, i.e., a phospholipase inhibitory protein, while GEF is a kallikrein-like enzyme. Specific aims of the current proposal are to determine possible roles of GIF and GEF in the immune responses. i) We shall establish antigen-specific T cell clones and T cell hybridomas which release IgE-suppressive factor upon antigenic stimulation, and determine whether GEF will switch the cells from the formation of IgE-suppressive factor to the formation of IgE-potentiating factor. ii) We shall determine whether carbohydrate moieties in IgG-binding factors may have important role in their biologic activities. iii) Recent experiments have shown that GIF released from antigen-specific suppressor T cells has affinity for antigen and bears I-J determinant(s). We shall characterize antigen-specific GIF, and compare this factor with antigen-specific suppressor factors. iv) We shall determine possible association of I-J determinants with lipomodulin, and investigate effects of anti-lipomodulin and anti-I-J alloantibodies on the IgE antibody responses. v) Our preliminary experiments have shown that GIF is immunosuppressive on the IgE and IgG antibody responses. Thus, we shall investigate mechanisms of immunosuppression. vi) Physicochemical and biochemical activities of GEF will be determined. vii) Since our preliminary experiments suggested that GEF is released from antigen-primed Ly 1+ T cells upon antigenic stimulation, and GEF from this source has affinity for antigen, we shall determine whether "antigen-specific" GEF might have some relationship to antigen-specific augmenting factor. viii) We shall determine possible effects of monoclonal anti-GEF on the IgE antibody formation.